Synthesis Characterization and Evaluation of Biological Activity of Vinylchromones and Biphenyls

Abstract

The present thesis comprises the design and synthesis of 2-vinylchromone and biphenyl derivatives and identification of bioactivity profile, particularly as anti-breast cancer agents alongwith antioxidant and antimicrobial agents. newlineIn the present study, we have primarily evaluated novel derivatives of 2-vinylchromones and biphenyls as possible SERM s. SERM s are selective estrogen receptor modulator used in the treatment of estrogen receptor (ER) positive breast cancer. Molecules that exhibit ER subtype selectivity can possibly act as SERMs. ERand#945; and ERand#946; are estrogen receptor subtypes. The ligand binding domain (LBD) of ERand#945; and ERand#946; have 53% homology. Literature indicates difference in two amino acid residues i.e. Leu384 in ERand#945; corresponding to Met336 in ERand#946; and Met421 in ERand#945; corresponding to Ile373 in ERand#946; which leads to the differences in overall volume of LBD of ER. This can form the basis for design of ligand that exhibit ER subtype selectivity. Furthermore, previous studies have also indicated that the presence of basic flexible side chain contributes to non-productive position of helix 12 (H12) of ER leading to arrest of transcriptional response. Based on the above premise and pharmacological significance of chromones and biphenyl scaffolds, prompted us to synthesize novel derivatives of these scaffolds and evaluate the contribution of flexible side chain, basic side chain and stereochemistry incorporated in the 2-vinylchromone and biphenyl scaffolds for SERM activity. Additionally, the synthesized derivatives were also evaluated for antioxidant and antimicrobial activity. newline